Agranulocytosis - a change in the picture of peripheral blood, which develops in a number of independent diseases and is characterized by a decrease in the number or disappearance of granulocytes. In hematology, agranulocytosis means a decrease in the number of granulocytes in the blood of less than 0.75x109 / l or a total number of leukocytes below 1x109 / l. Congenital agranulocytosis is extremely rare; The acquired condition is diagnosed with a frequency of 1 case per 1200 people. Women suffer from agranulocytosis 2-3 times more often than men; Usually the syndrome is detected at the age of over 40 years. Currently, in connection with the widespread use of cytotoxic therapy in medical practice, as well as the emergence of a large number of new pharmacological agents, the incidence of agranulocytosis has increased significantly.
First of all, agranulocytosis is divided into congenital and acquired. The latter can be an independent pathological condition or one of the manifestations of another syndrome. The leading pathogenetic factor distinguishes between myelotoxic, immune haptenic and autoimmune agranulocytosis. Idiopathic (genoinous) form with an unknown etiology is also distinguished.
According to the peculiarities of the clinical course differentiate acute and recurrent (chronic) agranulocytosis. The severity of the course of agranulocytosis depends on the amount of granulocytes in the blood and can be mild (at a granulocyte level of 1.0-0.5x109 / L), medium (at a level less than 0.5x109 / L) or severe (with no granulocytes in the blood).
Granulocytes are called leukocytes, in the cytoplasm of which the specific granularity (granules) is determined during staining. Granulocytes are produced in the bone marrow, so they belong to the cells of the myeloid series. They form the largest group of leukocytes. Depending on the characteristics of granule staining, these cells are divided into neutrophils, eosinophils and basophils - they differ in their functions in the body.
The share of neutrophilic granulocytes accounts for up to 50-75% of all white blood cells. Among them, there are mature segment-nuclear (in the norm of 45-70%) and immature stab neutrophils (in the norm 1-6%). A condition characterized by an increase in the neutrophil count is called neutrophilia; In the case of a decrease in the number of neutrophils, neutropenia (granulocytopenia) is indicated, and in the absence of neutrophils, agranulocytosis. In the body, neutrophilic granulocytes act as the main protective factor against infections (mainly microbial and fungal). When the infectious agent is introduced, the neutrophils migrate through the wall of the capillaries and rush into the tissue to the foci of infection, phagocytize and destroy the bacteria with their enzymes, actively forming a local inflammatory response. With agranulocytosis, the body's response to the introduction of an infectious agent is ineffective, which can be accompanied by the development of fatal septic complications.
Myelotoxic agranulocytosis occurs due to suppression of the production of myelopoiesis progenitor cells in the bone marrow. At the same time in the blood there is a decrease in the level of lymphocytes, reticulocytes, platelets. This type of agranulocytosis can develop with exposure to the body of ionizing radiation, cytostatic drugs and other pharmacological agents (levomycetin, streptomycin, gentamicin, penicillin, colchicine, aminazine), etc.
Immune agranulocytosis is associated with the formation of antibodies in the body, the action of which is directed against its own leukocytes. The emergence of haptenic immune agranulocytosis provokes the administration of sulfonamides, NPVS-derivatives of pyrazolone (amidopyrine, analgin, aspirin, butadione), drugs for the therapy of tuberculosis, diabetes mellitus, helminthiases that act as haptens. They are able to form complex compounds with blood proteins or leukocyte envelopes, becoming antigens, against which the body begins to produce antibodies. The latter are fixed on the surface of white blood cells, causing their death.
At the heart of autoimmune agranulocytosis is the pathological reaction of the immune system, accompanied by the formation of antineutrophil antibodies. This type of agranulocytosis occurs in autoimmune thyroiditis, rheumatoid arthritis, systemic lupus erythematosus and other collagenoses. Agranulocytosis, which develops in certain infectious diseases (influenza, infectious mononucleosis, malaria, yellow fever, typhoid fever, viral hepatitis, poliomyelitis, etc.) also has an immune character. Severe neutropenia can signal chronic lymphocytic leukemia, aplastic anemia, Felty's syndrome, and also occur in parallel with thrombocytopenia or hemolytic anemia. Congenital agranulocytosis is a consequence of genetic disorders.
Pathological reactions accompanying the course of agranulocytosis are in most cases represented by ulcerative necrotic changes of the skin, mucous membrane of the oral cavity and pharynx, less often - conjunctival cavity, larynx, stomach. Necrotic ulcers can occur in the intestinal mucosa, causing perforation of the intestinal wall, the development of intestinal bleeding; In the wall of the bladder and vagina. At microscopy of sites of a necrosis absence of neutrophilic granulocytes is found out.
Clinic of immune agranulocytosis usually develops sharply, in contrast to myelotoxic and autoimmune variants, in which pathological symptoms arise and progress gradually. The early manifest manifestations of agranulocytosis include fever (39-40 ° C), severe weakness, pallor, sweating, arthralgia. Characteristic ulcerative and necrotic processes of the mucous membrane of the mouth and pharynx (gingivitis, stomatitis, pharyngitis, sore throats), necrosis of the tongue, soft and hard palate. These changes are accompanied by salivation, sore throat, dysphagia, spasm of chewing musculature. There is regional lymphadenitis, a moderate increase in the liver and spleen.
For myelotoxic agranulocytosis, the appearance of a mild hemorrhagic syndrome, manifested by gum bleeding, nasal bleeding, bruising and hematoma, is typical. When the intestine is affected, necrotic enteropathy develops, manifestations of which are cramping pains in the abdomen, diarrhea, bloating. In severe form, complications can occur in the form of perforation of the intestine, peritonitis. With agranulocytosis in patients, hemorrhagic pneumonia can occur, complicated by abscesses and gangrene of the lung. In this case, the physical and radiological data are extremely scarce. Among the most frequent complications are possible perforation of the soft palate, sepsis, mediastinitis, acute hepatitis.
A group of potential risks for the development of agranulocytosis are patients who have had a serious infectious disease receiving radiation, cytotoxic or other drug therapy, suffering from collagenoses. From the clinical data, the diagnostic value is represented by a combination of hyperthermia, ulcerative and necrotic lesions of visible mucous membranes and hemorrhagic manifestations.
The most important for confirmation of agranulocytosis is the examination of the general blood test and bone marrow puncture. The picture of peripheral blood is characterized by leukopenia (1-2x109 / l), granulocytopenia (less than 0.75x109 / l) or agranulocytosis, moderate anemia, with severe degrees - thrombocytopenia. In the study of the myelogram, a decrease in the number of myelocaryocytes, a decrease in the number and disruption of the maturation of neutrophilic germ cells, the presence of a large number of plasma cells and megakaryocytes. To confirm the autoimmune nature of agranulocytosis, antineutrophil antibodies are determined.
All patients with agranulocytosis are shown lung radiography, repeated blood tests for sterility, a biochemical blood test, a consultation with the dentist and an otolaryngologist. Differentiate agranulocytosis from acute leukemia, hypoplastic anemia. It is also necessary to exclude HIV status.
Patients with verified agranulocytosis should be hospitalized in the department of hematology. Patients are placed in an isolation ward with aseptic conditions, where regular quartzing is carried out, visits are limited, medical personnel works only in hats, masks and shoe covers. These measures are aimed at preventing infectious complications. In the case of development of necrotic enteropathy, the patient is transferred to parenteral nutrition. Patients with agranulocytosis require careful care of the oral cavity (frequent mouth rinses with antiseptic solutions, lubrication of mucous membranes).
The therapy of agranulocytosis begins with the elimination of the etiologic factor (the abolition of myelotoxic drugs and chemicals, etc.). To prevent purulent infection, unabsorbed antibiotics, antifungal agents are prescribed. The intravenous introduction of immunoglobulin and antistaphylococcal plasma, transfusion of leukocyte mass, with hemorrhagic syndrome - platelet mass was shown. In the immune and autoimmune character of agranulocytosis, glucocorticoids are prescribed in high doses. When there is a CEC and antibodies in the blood, plasmapheresis is carried out. Stimulants of leukopoiesis are used in complex treatment of agranulocytosis. Prevention of agranulocytosis, mainly, is the conduct of thorough hematological control during the course of treatment with myelotoxic drugs, exclusion of re-administration of drugs that previously caused the phenomenon of immune agranulocytosis in the patient. An unfavorable prognosis is observed with the development of severe septic complications, the repeated development of haptenic agranulocytosis.